Project Summary The goal of this proposal is to investigate the role of a novel Telomere associated protein that we termed TZAP in telomere homeostasis. Telomeres are essential nucleoprotein structures that cap chromosome ends. Alterations in telomere function are associated with various human diseases including cancer, premature aging, dyskeratosis congenita, aplastic anemia, and idiopathic pulmonary fibrosis. Our preliminary data show that TZAP is a novel telomere specific binding protein that is involved in telomere length homoeostasis. Several questions remain to be addressed to define the role of this novel telomere associated protein in telomere homeostasis. To address this questions, we have devised a research proposal that will define the mechanism of TZAP binding to telomeres, its role on telomere length regulation and the impact of its depletion in respect to genome stability and tissue homoeostasis.